Genes encoding ACE2, TMPRSS2 and related proteins mediating SARS-CoV-2 viral entry are upregulated with age in human cardiomyocytes.

Abstract

Age (>70 years), case fatality rate (CFR,10.2%) and coexisting conditions, particularly cardiovascular disease (CFR,10.5%) and hypertension (CFR,6.0%), are independent predictors of adverse outcome for 45,000 COVID-19 patients in China [1]. A consensus has emerged that SARS-CoV-2 uses the same ‘receptor’ as SARS-CoV, the angiotensin converting enzyme 2 (ACE2), for initial binding to the host cell. This must be co-expressed with the serine protease TMPRSS2, that primes the spike protein S1 for endocytosis-mediated internalization of virus, employing the S2 domain for fusion to the host membrane (Figure [1A])[2-4]. A key difference in SARS-CoV-2 is a spike protein second site (S2’), proposed to be cleaved by the proteinase furin2. Once inside the cell cysteine proteases, cathepsin L and B, are thought critical for endosomal processing in certain cells [3-4]